This new proposal consists of biochemical and histological approaches to the mechanism of regulation of tissue collagenase. Our main aim is to gain new knowledge of tissue collagenase of bone and periodontal tissues in health and disease and the results will be of basic value in developing a method to control and prevent bone resorption, thereby preventing alveolar bone loss in periodontal disease. The objectives are: l. To study the latency of bone collagenase and the mechanism of its activation by isolating the enzyme, its latent form, inhibitor and activator. 2. To study the levels of tissue collagenase, in its active and/or latent forms of various cells and subcellular fractions derived from bone and periodontal tissues. Radioimmunoassay using specific antibody produced against mouse bone collagenase is our method of choice. 3. To study the possible capacity of anti-collagenase and other collagenase inhibitors to inhibit bone resorption in tissue culture in order to examine the role of this enzyme in the mechanism of bone resorption. 4. To study the rate of synthesis of collagen and collagenase in established fibroblast cell line, 3T6, and in isolated bone and gingival cells. The collagen synthesis is assayed as bacterial collagenase-digestible radioactive protein or by measuring labeled hydroxyproline after isolation by amino acid analysis and the amount of enzyme by radioimmunoassay.